This study is the first to assess combination immunotherapy in patients with metastatic urothelial carcinoma, said Padmanee Sharma, MD, University of Texas M.D. Anderson Cancer Center, Houston, at the 2016 Society for Immunotherapy of Cancer meeting.

A phase 2 study demonstrated efficacy for all subgroups of patients with metastatic urothelial cancer and PD-L1 expression. In other studies, clinical data with a combination regimen of nivolumab plus ipilimumab have shown improved antitumor activity in patients with advanced melanoma, non−small-cell lung cancer, or metastatic renal-cell carcinoma.

The CheckMate-032 Clinical Trial

In the CheckMate-032 clinical trial, 28 patients received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and 104 patients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 cycles; both treatment groups received maintenance therapy with nivolumab 3 mg/kg every 2 weeks. The primary end point was investigator-assessed overall response rate that was confirmed by Response Evaluation Criteria in Solid Tumors version 1.1.

Overall, 50% of patients who received the nivolumab 1-mg/kg plus ipilimumab 3-mg/kg regimen had a median age of ≥65 years versus 45.2% of patients who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. In both treatment groups, approximately 60% of patients received ≥2 previous regimens, and 88.5% of patients had visceral metastases. PD-L1 expression was ≥1% in 38.5% of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg compared with 28.8% of patients who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg.

“It’s very important to note the overall response rate compared to the 19% with nivolumab monotherapy reported in the Lancet Oncology, and the 15% rate previously reported for atezolizumab [Tecentriq]. Historical controls are 10% or less,” said Dr Sharma.

Although the cohort size is small, these findings are “very promising,” she emphasized, noting that the nivolumab monotherapy findings had previously been reported (Sharma P, et al. Lancet Oncol. 2016;17:1590-1598), she said.

Practical Implications

In response to a question regarding the possible benefit of using ipilimumab 10 mg/kg, Dr Sharma noted that “with ipilimumab 3 mg/kg, you get the same T-cell activation as with ipilimumab 10 mg/kg. Our monitoring showed, however, that ipilimumab 1 mg/kg does not give you the same level of T-cell activation as with 3 mg/kg, which would not give you the same level of antitumor response.”